VDU's blog: Congenital Zika syndrome

Showing posts with label Congenital Zika syndrome. Show all posts

Tuesday, 5 July 2016

Brazil's microcephaly and CNS disorder (M&CD) monitoring: Report No. 32, 2016-Week No. 25...

These graphs are made by me using data obtained from epidemiological week (EW) number 25's Brazil Ministry of Health microcephaly and foetal and infant microcephaly and central nervous system (CNS) disorders (M&CD) report.[1]

Brazil last reported a total of 120,161 suspected Zika virus detections some weeks back. Around one thousand of these have been confirmed.[2,3]

Suspected M&CD cases...

The total number of suspected M&CD cases increased by 126 to 8,165 this EW (compared to last).

The graph above shows the number of suspected M&CD diagnoses in Brazil up to 25-June-2016. The cumulative curve (yellow dots; left hand axis) is growing, but slowly.

This was another weekly rise (orange bars; right-hand axis). These bars are based on the difference in total suspected cases reported this EW compared to that reported in the last EW. This method may not reflect the diagnoses that occurred during the past EW (some may have come from days or weeks earlier), but that level of detail is not available in the MOH report.

Confirmed and discarded M&CD diagnoses...

M&CD cases under investigation increased by 54 to 3,061 this week.

In the graph above, we can see that 50 (blue bars; right hand axis) suspected M&CD diagnoses were discarded upon closer investigation with a current total of 3,466 removed.

The rate of these resolved diagnoses (line with blue dots, left-hand axis) seems similar to the rate of the smaller overall number of confirmed M&CD diagnoses (red dots, left-hand axis).

As of this EW, 20% of suspected M&CD diagnoses have been confirmed while 42% of suspected diagnoses have been discarded-a percentage that has been steady for 4 EWs.

The cumulative number of confirmed M&CD diagnoses does continue its climb this EW, growing by 22 new diagnoses (red bars; right-hand axis) to total 1,638.

The number of these M&CD diagnoses to be confirmed with a Zika virus infection also grows (green dots; left-hand axis) by 37 new detection (green bars; right-hand axis) to 270 this EW after rising by 7 the preceding EW.

Those confirmed Zika virus infections represent 16% (an increase for the first time about 11 weeks) of all confirmed M&CD diagnoses and 3% of all suspect diagnoses.

References...

Monday, 30 May 2016

Microcephaly, calcium deposits and eye problems...

What do virologists do when they are holed up at home with a productive cold? No idea. But I'm doing some reading of stuff I don't know much about; some historic literature on microcephaly.

I thought the slightly edited quote below, was interesting.[1]

Historic articles describing eye issues in microcephaly diagnoses are also interesting.[2,5] These are in light of similar language describing Brazilian microcephaly diagnoses as being part of a distinct or a unique syndrome.[3,4]

This does beg the question of how well we've catalogued microcephaly's features in the past? With new and emerging technologies and techniques always adding new ways of looking at disease, perhaps we're due for an update.

This is all well outside my area of expertise so take it with a huge grain of salt, but perhaps some of the current event is rediscovery, or even new discovery of something that is not unusual, just not previously captured among microcephaly diagnoses due to genetic issues, other infections or environmental influences?

It would be helpful to see some modern comments/reviews around this topic from experts in this field.

References..

Sunday, 22 May 2016

Zika in the mouse...

Just over a week ago there were a few published Zika virus (ZIKV) studies in mice and brain balls (neurospheres and organoids). These were big deals. One was a letter to Nature by Cugola and colleagues, describing defects in the brains of mouse pups after their mothers were infected with virus.[1] This was one big letter and well outside my expertise to review in any sort of depth. But it raised a few questions for me.

Briefly, there were two parts to the letter - in part 1, two lines of pregnant mice (SJL and C58BL/6) were injected with virus and the pups evaluated immediately after birth. In Part 2, cell culture created human progenitor stem cells (hPSCs) and brain balls (neurospheres and cerebral organoids) were incubated with ZIKV.

This study included a ZIKV variant currently circulating in Brazil (ZIKV^BR) rather than using the virus from six decades ago, but disappointingly, it did not include dengue virus or Chikungunya virus as control viruses against which to compare the activities described for ZIKV. There was some use of a slow-growing, attenuated (low risk of nerve pathology) vaccine strain of yellow fever virus as control virus - but exactly how wasn't clear to me. There was no virus control in the mouse work though - just the organoid experiments - as far as I can tell.

One big takeaway message was that the C56BL/6 pups did not have any notable differences compared to healthy pups. Virus did not seem to cross the placenta. All the problems found were in the other line of mice - the immunologically defective SJL.[8,9]
The authors note the C56BL/6 line had a robust antiviral immune response.
If ZIKV is indeed the cause of congenital disease in humans, there is something to that result that should be of much interest. Whether that is at the level of a genetic immune deficiency, a microbiome-level issue or the occurence/history, absence or order of past infections, among other things, is unclear
The SJL pups were smaller, had lots more ZIKV RNA in the brain than in kidney, liver or spleen, tissues, had eye abnormalities and had elevated markers suggesting that brain cell death was linked to apoptosis and autophagy. The authors remarked how these shared similarities with foetal human disease
I have my usual question about how relevant to a human is a model that directly introduces a dumpload of virus into the blood (40,000,000,000 plaque forming units) by injection when the natural route of infection of a human is considered to be mostly due to a (presumably) much lower load from mosquito bite. Adding the same dose of inactivated ZIKV would have been very interesting to test for non-viral effects from the inoculum (h/t KatA)
Human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs) were also exposed to virus and found to die via apoptosis. But where did these cells originate? I can't tell from the methods and references cited. Was it from human skin cells as other experiments have used? Skin cells are known to host ZIKV [3] Could this be a confounding factor?
Mock infected NPCs - "pretend" infection in the absence of any actual virus to check whether the method or material carrying the virus caused the observed damage - actually upregulated expression of the likely receptor for ZIKV, AXL, but ZIKV infection didn't. Does that mean ZIKV down-regulated expression caused by something in the mock inoculum?
High doses (10 MOI) of ZIKV killed NPCs, but a lower dose (1 MOI) did not - what does that mean for the heavily dosed mouse model; and for a human bitten by a mosquito? ZIKV^BR and an African lineage ZIKV (ZIKV^AF) acted similarly.
In three dimensional cultures, neurospheres growing in the presence of 10 MOI of ZIKV^BR were smaller and cell death was apparent - the effect was not as strong with ZIKV^AF suggesting lineage differences. Effects were dose dependent - stronger with higher doses (10 MOI) than lower (1 MOI). Differences between ZIKV lineages is something yet to be fully explored by virology-for some inexplicable reason(s).

You'll possibly have noticed two units used by the authors - plaque forming units and MOI (multiplicity of infection). These are different because of different methods used to determine the endpoints. Briefly (but still technically):

From Sloutskin et al.[6]

For plaque-forming units (PFU) - we titrate infectious virus that can damage cells (make plaques) and look at where the effect finishes. By titrate I mean serially dilute and then add each diluted solution to a separate well of the same cells, usually grown in a multiwell plate. The effect is the formation of plaques - areas of clearing due to virus-induced death of cells that had first been grown into a single layer in each plate well before being infected by a virus preparation. The dilution before the effect finishes is the PFU.
There are also issues around how well PFU value determined using one cell culture model holds up when infecting a cell/tissue/organ/animal that is different from the one you determined your PFU on - you may get different results.
For example you may find your virus preparation contains 10,000 PFU on the original cells, but if you did that same titration with the same preparation but using a different cell type, it may contain 100,000 PFU or 1,000 PFU.
In the study above, ZIKV was grown up using a C6/36 mosquito cell line, then titrated using porcine kidney epithelial cells to determine the PFU then that C6/36 preparation was used for the mouse, NPC, neurosphere and organoid incubations. This is normal approach but can raise questions.
For multiplicity of infection (MOI) we are talking about the average number of virus particles in a preparation that infect a target cell. 1 MOI means 1 virus particle per cell. An MOI of 10 means 10 virus particles per cell.[4] This works well in cell culture where we often use a single cell type grown in a single layer - conditions, viral density and culture volumes are optimized and we use the same cells as for the PFU.[5] When you take that MOI of 1, calculated on your cell line, and add it to a different and complex tissue, or animal, with lots of different cell types, perhaps spread over a larger or smaller surface, in the presence or absence of an antiviral response, with more or fewer receptors etc...the ratio of 1 virus : 1 cell will probably not hold up. So using a higher MOI makes it more likley that each cell in a different tissue/organ/animal will get infected. Thus an MOI of 1 and 1 PFU are not always the same thing. A virus preparation determined to have an MOI of 1 using one system might require 0.1 or 273.64 PFU of that preparation in another cell/tissue/organ/animal system, because it takes that amount to finally show the desired effect (cell death, PCR positivity, virus protein detection etc) in that target cell/tissue/organ/animal.

We should also think about how relevant an MOI of 10 is to the thing we originally sought to study. In this case it is the early brain structure of a foetus whose mother was infected from a mosquito bite.
The bite itself would not have delivered anything like an MOI of 1 to any tissue in that mother's body.
But how much ZIKV crosses the human placenta in the rare cases that it does at all? Well, we assume placental crossing is a rare event for ZIKV.
I'd presume it's also not an MOI of 1 for any tissue in the foetus - unless the placenta is where the virus is being amplified. But it does seem like there is a lot of ZIKV in the brain of studied infected foetuses. So this mouse model might reflect what happens in a forming human brain that amplifies virus it acquired after placental crossing, or that was present from conception (here for more on that theory[7]).

One of my biggest questions about this study is - so what?

This is an incredibly dense and impressive piece of work - don't get me wrong. It may well be the definitive result that so many have commented on it being. But I wonder if the same degree of very detailed investigation gone into the study of other mosquito-borne viruses in mouse brains? Have we sought out the congenital infection potential of other arboviruses in mouse pups and investigated arbovirus impact on neurospheres and organoids to this extent? Are these results unique to ZIKV or do the same or similar effects from other viruses, that - to our knowledge - are not considered threats for congenital disease in humans? We should probably establish that, by using more experimental controls, before we continue on our journey along this limb.

I have trouble saying that this experiment equals that disease as much as I am troubled by saying that the (possible) surge of microcephaly diagnoses in north east Brazil is caused by that particular parallel viral epidemic.

References...

Monday, 25 April 2016

Did Zika virus detections peak in Colombia during Week #3 2016?

Does the graph below, taken from the Colombian Ministry of Health's latest (Week No. 15) epidemiological report, signal that Zika virus detections (red bars; laboratory confirmed) peaked in Week No.3 of January-2016?

Excerpted from [1].

If it does, then we should add to the hypothetical list [2] of reasons why there is not yet any surge of microcephaly and central nervous system disorder diagnoses (M&CD) in Colombia - the country with the second biggest reported number of Zika virus detections - that we may have to wait for at least 184 days from Week No.3 (give-or-take, obviously).

In other words, around Week No.29 we may see an equivalent surge in M&CD diagnoses in Colombia....all other things being equal between the two countries (which they likley are not) and if Zika virus is the driving cause of M&CD. This graph comes from Week No.15.

Why 184 days? Only because that was the length of time between when Brazil first reported local (autochthonous) transmission of Zika virus and its first report of the possibly linked M&CD surge (in which it bundling 141 cases up in one announcement).[3]

Yeah, it's a flexible number to be sure but it is what it is, and it's more solid than some of the data flying around.

Worth watching anyway.

References...

Sunday, 24 April 2016

Colombia Zika virus report, Week No. 15...

The latest epidemiological report, which includes data on Zika virus disease (ZVD; 10APR2016-16APR2016), has been produced by the Colombian National Institute for Health team.[1]

Graph No.1. The cumulative curve of confirmed ZVD cases

(green circles, left-hand axis) and the change in confirmed ZVD case

numbers when compared to the preceding week's total

(green bars, right-hand axis). Data from [1].

Click on graph to enlarge.

Graph No. 1 shows that zero new laboratory confirmed cases of ZVD reported this week. The total holds steady at 3,292 or 5% of all the clinically suspected Zika virus (ZIKV) detections. I wonder if this is further support for a theory that there is a lag in laboratory reporting in Colombia, or was there was no testing conducted (seems unlikely)?

Graph No.2. The cumulative curve of suspectedZVD cases

(pink circles, left-hand axis) and the change in suspected ZVD case

numbers when compared to the preceding week's total

(red bars, right-hand axis). Data from [1].

Click on graph to enlarge.

Graph No. 2 shows the change in suspected cases. Most of these are not laboratory confirmed, but (I'm presuming here) include those that were from Graph No. 1. The suspected ZVD cases keep accumulating - another 3,059.

Graph No.3. The cumulative curve of confirmed ZIKV infections

(lilac circles, left-hand axis) and the change in confirmed ZIKV infection

numbers when compared to the preceding week's total

(purple bars, right-hand axis). Now added the reported umber of microcephaly cases

confirmed as ZIKV infected (yellow bars, right-hand axis). To account for adjustments

that take cases away when there is no weekly case growth, a negative

value - the y-axes now allow for negative values. Data from [1].

Click on graph to enlarge.

Graph No. 3 shows that to Week No. 15, 11,099 suspected and 1,703 confirmed ZIKV infections have been identified in pregnant women. Last week there were 1,706 confirmed diagnoses so the purple bar for this week strays into negative territory (-3 compared to last week).

As of this report, 4 (increased by 2 from last week) live births have been diagnosed with microcephaly/central nervous system disorders and were reported as being ZIKV positive; 22 (up from 15) other microcephaly diagnoses are under investigation.[1]

References...

http://www.ins.gov.co/boletin-epidemiologico/Boletn%20Epidemiolgico/2016%20Boletin%20epidemiologico%20semana%2015.pdf

Saturday, 23 April 2016

On Zika and microcephaly: causality, consensus and checklists....

Over the past month the World Health Organization (WHO) and then the United States Centers for Disease Control and Prevention (CDC) have associated infection of by Zika virus (ZIKV) with cases of microcephaly and central nervous system disease (M&CD).[1]

The first WHO statement cited a scientific consensus identified at a meeting called to examine the evidence linking ZIKV infection with foetal malformations and neurological disorders.[1] Later in March the WHO pointed to case studies as the origin for that scientific consensus.[2] I've talked about my views on gaps in some of these studies before - for example here and here.

The CDC based their much stronger comments on a review of the literature and its application to address historically robust checklists - Shepard's criteria and the Bradford Hill criteria - that have heretofore proven themselves useful to identify teratogens (causes of embryonic malformation).[3] The CDC authors of this paper note that there is no "smoking gun" at this point and Dr Tom Frieden, CDC Director said it could take years before answers to other questions are found.[12] But not about ZIKV causing microcephaly. That question is answered according to two of the world's leading public health agencies.

Checking the checklists.

The checklists CDC used were applied to resolve the questions around the cause of an apparent surge of M&CD diagnoses - the so-called congenital Zika syndrome.[4,5] To date this has been almost exclusively occurring in north east Brazil. Some instances have been reported in other countries with current - or past - ZIKV epidemics, but the numbers are small enough for questions to linger about whether these represent part of "normal" M&CD figures, perhaps brought to attention because of the enhanced focus on congenital deformities in 2015 and 2016 or ZIKV-caused disease.

Shepard noted in 1994 that..

"the rare malformation/rare exposure
or case report method is far easier,
less expensive, and more common than
full epidemiologic studies."

He described "Examples of this rare defect/rare exposure "proof" (or better stated strong association)"[sic] including the virus driven congenital rubella. I'm not sure about rare in terms of ZIKV infection tough. While data are near on-existent from Brazil, we've been told that over a million people have been infected with ZIKV.[19] That seems to be a much less stringent use of Shepard's criteria than that of the CDC's "no longer any doubt".[12] Shepard's criteria have gone on to be used in legal definitions [7] which also take a broader view on causality in the study of teratology..

"causation is demonstrated between an
exposure and an outcome if the outcome
would not have occurred but for the exposure.
The but-for test is typically modified by a
substantial factor test, that is, the
exposure was a substantial factor in
bringing about the outcome, or by
consideration of the exposure as a
contributory cause"

The other checklist was the tabulated criteria of Bradford Hill, described in 1965 in his occupational medicine-focussed paper, The Environment and Disease: Association or Causation? which sought to relate sickness, injury and conditions of work.[18] I find Bradford Hill's comments in the Experiment section of his criteria interesting as they discuss whether a preventative action in fact reduces the frequency of the event...

"Here the strongest support for the
causation hypothesis may be revealed."

The CDC interpret this wholly in relation to an animal model.[3] Perhaps this meaning has evolved in subsequent analyses that I admittedly haven't read, but I see this criterion differently. To me it is addressing the need to wait and watch for any impact on reduced mosquito breeding and presence either because of seasonal variation or human interventions; a long wait.

In a statement similar to Koch's about his postulates, Bradford Hill stresses that none of these criteria can be used as if they were set in stone and none bring indisputable evidence for or against a cause-and-effect hypothesis. They are intended to..

"help us to make up or mins on the fundamental
question - is there any other way of
explaining the set of facts before us, is
there any other answer equally, or more,
likely than cause and effect?"

This seems - to me at least - at odds with the CDC's strident use of these criteria to define causality here.

Neither checklist necessarily hits the mark perfectly for what we're seeing in Brazil but, as with Koch's original postulates, these have been "matured" and tuned over time to fit the need of the moment-presence of a common virus infection causing a rare syndrome.

Is the strong language essential to a response?

But let's back quietly out of the courtroom and return to the world of science, research and causality. We don't have a smoking gun but that has not prevented some important triggers being pulled. Principal among these was that the WHO called a Public Health Emergency of International Concern (PHEIC) on the 1st of February 2016.[8] Well before the need to use stronger language in March 2016, the PHEIC generated recommendations [9] for...

To interrupt ZIKV transmission using enhanced surveillance, diagnostics, risk communication, vector control measures, counselling and more
research and develop vaccines, therapeutics and diagnostics and increases relevant services in affected areas
provide uptodate advice on travel to affected areas, disinfection of aircraft but do not restrict travel or trade
ensure rapid and timely reporting and sharing of information of public health importance relevant to the PHEIC

Obviously those things are expensive. We know from recent experience that the WHO struggled to get the pledged funds they'd requested to mount for an effective Ebola virus disease reposes fast enough and to match the requested spend. Perhaps stronger language is intended to free up the purse strings.[10,11] The main ~~sigh of relief~~ outcome from making such a strong statement by the CDC was...

"Now that we've determined the causal the
relationship, we can use this information to
redouble our efforts to prevent Zika, more
narrowly focus our research and communicate
even more directly about the risks of Zika."

And herein lies one of my concerns. Narrowed research, by definition, could miss things that have contributed to congenital Zika syndrome. Things that might include...

other viruses - rubella and cytomegalovirus are teratogenic viruses that are sometimes sought and not often found but that search can use a hodgepodge of methods. But what about new viruses and new variants of existing viruses?
the impact of chemicals or toxins - the pesticide issue has not gone away [13]
the very complex immune responses that to date have mostly been a topic for discussion as a problem for antibody detection in the lab, but may be a part of the process [14,16] although did not seem to play a role in Guillain-Barre syndrome [15]

But all those things may still be included in a narrowed research focus. Those things aside we do know that ZIKV loves to grow in epithelial cell-derived neural stem cells; there is a lot of IgM antibody to ZIKV in babies born with microcephaly [20] and ZIKV has been found in the brain tissues of foetuses with disease.[21]

Devil's advocate - what other things might we consider?

We have not yet addressed whether ZIKV is just as harmless as we used to think it was and whether it is found in these tissues as a passenger and not a pathogen.

Might it also be in the brain tissues of ZIKV-infected foetuses who do not develop any congenital anomalies? There has been little or no exploration of controls in most papers to date. Mostly - this would be unethical, but there might be other reasons for related tissues to be sampled which could then be leveraged fro important testing. Its important yet missing information.

Excerpted from WHO Zika virus microcephaly
and Guillain-Barre syndrome situation report. [17]

There is also the Colombian elephant in the room.

This week saw the number of M&CD diagnoses in Colombia double...okay, from 2 to 4... having decreased the week before. This might be normal and part of the 140 annual cases reported in Colombia annually-that's an average of 2.6 per week.

More time has now passed in Colombia than had in Brazil before Brazil reported its first concerns - and 141 M&CD diagnoses - over ZIKV and M&CD, after it identified local ZIKV transmission. As I've discussed previously, there could be many reasons for that difference - and a rise in cases in Colombia this week may herald that the starting line has been crossed indicating the beginning of some important supporting evidence for ZIKV causing M&CD. Or we might just be seeing normal levels of M&CD that also happen to be ZIKV infected-during an epidemic of ZIKV.

To my mind, the studies used to check off the lists leave some important things unanswered. Patience might have been advisable since the previous announcement of a PHEIC mean that there was no obvious need for the issue to be forced. Or perhaps this is more about the politics of finding a better way to secure the funding needed to address congenital Zika syndrome, and avoid the pitfalls of funding gaps dug during the fight to contain Ebola virus syndrome.

Only time will tell whether such strong WHO and CDC language was needed, helped or even hindered the response and understanding of congenital Zika syndrome.

References...

WHO Director-General briefs the media on the Zika situation
http://www.who.int/mediacentre/news/statements/2016/zika-update-3-16/en/
Zika situation report 31-March 2016
http://who.int/emergencies/zika-virus/situation-report/31-march-2016/en/
Zika Virus and Birth Defects — Reviewing the Evidence for Causality
http://www.nejm.org/doi/full/10.1056/NEJMsr1604338
http://www.bbc.com/news/world-latin-america-35763232
http://annals.org/article.aspx?articleid=2498549
"Proof" of Human Teratogenicity
http://onlinelibrary.wiley.com/doi/10.1002/tera.1420500202/pdf
Causation in Teratology-Related Litigation
https://www.teratology.org/pubs/Causation_Ter-Rl_Litigation.pdf
http://www.who.int/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/
http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/
http://www.globalissues.org/news/2016/02/01/21800
http://www.oxfam.org.uk/media-centre/press-releases/2016/01/international-community-fails-west-africa-yet-again-ebola
http://www.cdc.gov/media/releases/2016/t0414-zika-update.html
https://peerj.com/preprints/1959/
http://www.sciencemag.org/news/2016/03/qa-scott-halstead-zika-will-subside-5-years-max
http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf
https://www.statnews.com/2016/02/17/zika-dengue-infections/
http://apps.who.int/iris/bitstream/10665/205505/1/zikasitrep_21Apr2016_eng.pdf?ua=1
The Environment and Disease: Association or Causation?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1898525/pdf/procrsmed00196-0010.pdf
http://www.reuters.com/article/us-health-zika-brazil-exclusive-idUSKCN0VA331
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30253-7/fulltext?rss=yes
http://www.nejm.org/doi/full/10.1056/NEJMe1601862?af=R&rss=currentIssue

Thursday, 21 April 2016

Zika virus: ask questions....

The World Health Organization WHO) finally opened up the AskZika hashtag a week ago. Sadly, it has not been staffed to the extent that #AskEbola was, so little interaction is happening at this stage.

Nevertheless, here are the first questions I asked...

Hi @WHO
Is 80% "asymptomatic #Zika" based on Yap island household study or something more recent?
How robust is the figure? #AskZika
— Ian M Mackay, PhD (@MackayIM) April 15, 2016

Hi @WHO,
s there *any* evidence for/against mild or subclinical #Zika cases having any viraemia? #AskZika
— Ian M Mackay, PhD (@MackayIM) April 15, 2016

Is there any correlation between *symptomatic* #Zika virus disease and pre-existing #Dengue virus antibodies? #AskZika
— Ian M Mackay, PhD (@MackayIM) April 14, 2016

Are there current investigations into animal reservoirs for #ZikaVirus in the Americas?#AskZika #Zika
— Ian M Mackay, PhD (@MackayIM) April 13, 2016

Are there yet any confirmations of which mosquito species (single and plural) carry #ZikaVirus in the Americas? #AskZika #Zika
— Ian M Mackay, PhD (@MackayIM) April 13, 2016

.@MackayIM because people get infected early in life and are then immune?
— Ian Goodfellow (@igoodfel) April 13, 2016

Thanks to Ian for reminding me of this likely reason to address the last question - I had a caffeine-free moment when asking this one!

Because Zika virus has been ticking along for over 60 years - that we know of - in African countries - the population of affected areas will already have some degree of immunity by due to constant exposures, which the current thinking says are unnoticed 80% of the time. My Yap island question above highlights my doubt about that figure though.

But Ian's response made me think - do we know that an asymptomatic or mild Zika virus infection of a women produces enough immunity, and/or immunity of the right kind, to ensure that if she becomes infected by Zika virus a second time and she is pregnant, she could not deliver a child with central nervous system disease? We don't. Presumably, even with a population that has "seen" more Zika virus circulating, there would still be cases of adult women being infected for the first time and, if Zika virus is the cause, microcephaly resulting. Perhaps this has simply been lost in the background health issues though. Or perhaps something special, different or more complex is happening in Brazil that goes beyond Zika virus infection+pregnant woman=rare microcephaly case.

Congenital Zika syndrome is not reliably distinguished from other infective, toxic, or genetic causes of congenital anomalies, although others say the anomalies attributed to Zika virus infection outside the central nervous system are distinctive. This disagreement alone highlights how many questions this outbreak has raised and how few answers we've received.

Do you have questions about all this? Pose them to the #AskZika channel. Maybe we'll get some answers soon. We may at least get the scientific consensus of some answers, if that is satisfying enough for you.

Static pages

Tuesday, 5 July 2016

Monday, 30 May 2016

Sunday, 22 May 2016

Monday, 25 April 2016

Sunday, 24 April 2016

Saturday, 23 April 2016

Thursday, 21 April 2016